In his State of the Union address last
week, President Obama encouraged
the development of “precision
medicine,” which would tailor
treatments based on individuals’
genetics or physiology . This is an
effort to improve medical care’s
effectiveness, which might cause some
to wonder: Don’t we already have
effective drugs and treatments? In
truth, medical care is often far less
effective than most believe. Just
because you took some medicine for
an illness and became well again, it
doesn’t necessarily mean that the
treatment provided the cure.
This fundamental lesson is conveyed
by a metric known as the number
needed to treat, or N.N.T. Developed
in the 1980s , the N.N.T. tells us how
many people must be treated for one
person to derive benefit. An N.N.T. of
one would mean every person treated
improves and every person not
treated fails to, which is how we tend
to think most therapies work.
What may surprise you is that N.N.T.s
are often much higher than one.
Double- and even triple-digit N.N.T.s
are common.
Consider aspirin for heart attack
prevention. Based upon both
modifiable risk factors like cholesterol
level and smoking, and factors that
are beyond one’s control, like family
history and age, it is possible to
calculate the chance that a person will
have a first heart attack in the next 10
years. The American Heart Association
recommends that people who have
more than a 10 percent chance take a
daily aspirin to avoid that heart
attack.
How effective is aspirin for that aim?
According to clinical trials, if about
2,000 people follow these guidelines
over a two-year period, one additional
first heart attack will be prevented.
That doesn’t mean the 1,999 other
people have heart attacks. The fact is,
on average about 3.6 of them would
have a first heart attack regardless of
whether they took the aspirin. Even
more important, 1,995.4 people would
never have a heart attack whether or
not they took aspirin. Only one person
is actually affected by aspirin. If he
takes it, the number of people who
remain heart attack-free rises to
1996.4. If he doesn’t, the number
remains 1995.4. But for 1,999 of the
2,000 people, aspirin doesn’t make
any difference at all.
Of course, nobody knows if they’re the
lucky one for whom aspirin is helpful.
So, if aspirin is cheap and doesn’t
cause much harm, it might be worth
taking, even if the chances of benefit
are small. But this already reflects a
trade-off we rarely consider
rationally. (And many treatments do
cause harm. There is a complementary
metric known as the number needed
to harm, or N.N.H., which says that if
that number of people are treated, one
additional person will have a specific
negative outcome. For some
treatments, N.N.T. can be higher than
the number needed to harm,
indicating more people are harmed
than successfully treated.)
Not all N.N.T.s are as high as aspirin’s
for heart attacks, but many are higher
than you might think. A website
developed by David Newman, a
director of clinical research at Icahn
School of Medicine at Mount Sinai
hospital, and Dr. Graham Walker, an
assistant clinical professor at the
University of California, San
Francisco, has become a clearinghouse
of N.N.T. data, amassed from clinical
trials. Among them, for example, are
those for the effects of the
Mediterranean diet.
The Mediterranean diet, which is
heavy in vegetables, fruits, nuts and
olive oil; moderate in fish and poultry;
and light in dairy, meat and sweets;
has long been advocated as a means
to avoid heart disease . In people who
have never had a heart attack, but
who are at risk, the N.N.T. is 61 to
avoid a heart attack, stroke or death.
And that is for people who adhere to
the diet for about five years. For those
at higher risk, who have already had a
heart attack, to avoid one additional
death, the N.N.T. is about 30 . That’s
the number of people who would have
to adhere to the diet for four years so
that one extra person survived. About
1.4 people out of 30 such people will
die no matter what they eat; 27.6 will
not die no matter what they eat. Only
one will benefit from sticking to the
diet.
But it’s not easy for everyone to stick
to such a diet for that many years.
Some — for example, those who enjoy
steak and ice cream — will feel that it
diminishes their quality of life. When
you hear that the diet prevents heart
attacks, then it might sound worth it.
But does it still sound worth it when
you consider that 29 out of 30 people
who stick to the diet for several years
see no benefit at all? Will you stick to
it for years and be the lucky one for
whom that matters?
As treatments go, an N.N.T. of 30 is
pretty good. Very few are as low as 10,
though some are. For instance, the use
of steroids in people having asthma
attacks to prevent admission to the
hospital has an N.N.T. of eight . This is
so obvious, and so powerful a
treatment, that there are no
commercials and no op-eds preaching
steroid use for asthma. (Maybe there
should be. It’s likely that this therapy
is being underutilized, perhaps
because cost-sharing discourages some
people with asthma from seeking care
when they might need it.) Steroids
work very well for asthma attacks —
better than many treatments for other
conditions. But still, seven of eight
people suffering an asthma attack see
no benefit at all from steroids with
respect to preventing hospitalization.
Even more concerning, N.N.T.s as
calculated from clinical trial data are
probably lower than those based on
real-world medical care. In clinical
trials, treatments are applied to a
select population for whom they’re
intended. In medical practice, it’s very
common for treatments to be applied
to a much broader population,
including many people for whom
they’re less likely to be effective,
which increases the N.N.T. This is,
perhaps, because doctors would rather
offer an explicit treatment — perhaps
to harness a placebo effect — even
when it’s not likely to be of additional
benefit.
In fact, as recently reported in The
Times , a new study showed that many
people who are prescribed aspirin for
the primary prevention of
cardiovascular disease don’t meet the
criteria described above for its use.
Because of this use in a population
beyond that targeted in clinical trials,
the N.N.T. in practice is most likely
higher than the 2,000 suggested by
those trials. (It’s worth noting that our
best estimates of N.N.T.s can rise or
fall as more data are collected and as
treatments or how or to whom they’re
delivered change.)
Antibiotics are a classic example of
overuse. For instance, the N.N.T. for
antibiotics to treat radiologically
diagnosed acute sinusitis is 15,
meaning that 14 out of 15 who take
them derive no benefit. But physicians
often write prescriptions for
antibiotics in situations when the
diagnosis of sinusitis is far less
assured. This leads to antibiotics being
overprescribed and overused, raising
their N.N.T. in practice.
The use of stents to open up clogged
arteries in patients who are not
actively suffering a heart attack is
another treatment that is employed
too often. (Stents are considered
appropriate in patients who are
having a heart attack.) Many more
patients believe they extend life than
their N.N.T. suggests. The N.N.T is
effectively infinite, relative to
treatment with medications, for
people not suffering a heart attack.
Until health care technology improves,
there’s not a lot we can do about
N.N.T.s that are larger than we might
hope. It’s just a fact of current
medical technology that not everyone
benefits from treatment, even when
well targeted. President Obama’s push
for “ precision medicine ” is an attempt
to change this, by using genomics to
focus treatments on people who would
most benefit from them. That will take
time.
In the meantime, we would all be
better served by a more informed
understanding of exactly how much,
or how little, benefit is reasonably to
be expected by taking a drug,
changing our lifestyle or undergoing a
procedure. Especially since the chance
of benefit, as expressed by N.N.T.,
might not be worth the risk of harm,
as expressed by N.N.H. We’ll discuss
that more next week.
